Human recombinant interferon beta-1a (Megavex)

Hypoxia-inducible factor-1a (HIF1a) as a context-dependent integrator of metabolic stress in skeletal muscle.

Welch Nicole N, Kannan Pugazhendhi P, Pothabathula Seshu Vardhan SV, Bellar Annette A et al.

Skeletal muscle experiences large fluctuations in ATP demand and redox state during contraction, ischaemia and chronic disease, requiring rapid adaptations in substrate selection, mitochondrial workload, vascular coupling, regeneration and protein homeostasis. Hypoxia-inducible factor-1a (HIF1a) is classically viewed as an oxygen-responsive transcription factor that mediates rapid adaptation to hypoxia. Accumulating evidence across tissues, including skeletal muscle, indicates that HIF1a is also responsive to physiological and pathological inputs, such as exercise, circadian timing, redox perturbations and endogenous/exogenous cytotoxins, even when tissue hypoxia is not detectable. During hypoxia, including transient mismatches between oxygen demand and supply during muscle contraction, HIF1a activation shifts metabolism from oxidative to non-oxidative energy production, suppresses non-essential energy-consuming processes, including protein homeostasis, and promotes vascular responses that improve oxygen delivery. Under normoxic conditions, persistent HIF1a activation promotes maladaptive responses, including impaired mitochondrial remodelling, reduced anabolic responsiveness, defective regeneration, fibrosis, and atrophy- and senescence-associated reprogramming. Current evidence shows that this shift from adaptive to maladaptive signalling is determined in part by post-translational mechanisms that regulate signalling duration and target gene engagement, as well as by fibre type, circadian state and the nature of the upstream stressor. Unlike the robust responses in muscle tissue observed in preclinical models, human muscle biopsies often show modest or transient HIF1a accumulation, yet transcriptional responses indicate meaningful pathway activation, suggesting that biologically relevant signalling occurs even when total protein levels appear low. Genetic models, multiomics, and human studies support HIF1a as a context-dependent regulator of metabolic reprogramming that balances short-term adaptation with long-term energetic cost.

Correction: Postoperative adding-on phenomenon in Lenke 1A/B and 2A/B adolescent idiopathic scoliosis: risk factors and predictive index.

Zhang Hongqi H, Li Tao T, Zhang Gengming G, Deng Ang A et al.

Development of an inactivated, oral immunogenic product against post-weaning colibacillosis caused by enterotoxigenic Escherichia coli in piglets.

Inglesi Alessia A, Filipe Joel J, Valli Giulia G, Riva Federica F et al.

Post-weaning diarrhea (PWD) caused by enterotoxigenic Escherichia coli (ETEC) expressing F4 and F18 fimbriae remains a major challenge in pig production, contributing to economic losses and increased antimicrobial use. This study aimed to preliminary evaluate the immunogenic potential of an orally administered formulation comprising heat-inactivated ETEC strains expressing F4 and F18 fimbriae, combined with low-dose recombinant human interferon-alpha (IFN-α) as a mucosal adjuvant, in piglets. Piglets from two different litters were allocated into two experimental groups: a treated group (T) receiving the inactivated ETEC formulation with IFN-α for 26 days, and a control group (C) receiving only IFN-α. According to the farmer, the sows had not been vaccinated. Immune responses were evaluated in the sows colostrum and piglet serum, saliva, and feces by ELISA. In mesenteric lymph nodes anti-F4/F18 IgA and IgG antibodies were quantified by ELISPOT. The inactivated product preserved fimbrial antigenicity and remained sterile. Colostrum from both sows displayed elevated levels of fimbriae-specific IgA and IgG despite neither sow being vaccinated against E. coli. Treated piglets showed a transient serum IgA increase against F4 whereas serum IgG levels were often comparable to the controls. Notably, elevated mucosal IgA responses were observed in saliva and feces against both F4 and F18 (P < 0.01) in T group, accompanied by enhanced IgA-secreting B-cell activity in mesenteric lymph nodes. ELISA validation confirmed high assay reproducibility (R² > 0.98; CV < 10%). ELISPOT analysis underscored the adjuvant role of F4 and IFN-α in stimulating mucosal immunity. Our preliminary findings may represent a promising strategy to control PWD and reduce antimicrobial use in pig production.

Molecular Evidence of Human T‑Cell Leukemia Virus Type 1 Transmission by Needlestick Injury in Healthcare Workers.

Tokunaga Masahito M, Kuramitsu Madoka M, Saito Masumichi M, Yoshimori Miyuki M et al.

Human T‑cell leukemia virus type 1 (HTLV‑1) is a retrovirus that spreads primarily through cell-to-cell transmission. Occupational transmission of HTLV-1 by needlestick injury is considered exceedingly rare, with no reported molecularly confirmed cases. We report two healthcare workers who experienced accidental needlestick injuries while caring for patients seropositive for HTLV‑1 and subsequently seroconverted. Full‑length HTLV‑1 proviral sequencing revealed complete nucleotide identity between source patients and infected nurses. These strains belonged to the HTLV-1 subtype 1a Japanese subgroup but were distinct from 315 previously registered strains. Proviral integration site analysis demonstrated nonoverlapping integration profiles between source patients and healthcare workers, providing direct evidence of de novo HTLV‑1 infection rather than expansion of transferred infected cells. Longitudinal analysis in one case showed dynamic clonal turnover between 5 and 14 months after transmission; > 90% of infected-cell clones were replaced, although the proviral load remained stable and low. Serological profiling revealed transiently elevated immunoglobulin M responses to Gag p19 peptides during early infection, followed by gradual immunoglobulin G maturation. These findings provide the first molecular confirmation of HTLV‑1 transmission via needlestick injury resulting in de novo infection, revealing an under-recognized occupational exposure route and supporting reconsideration of post-exposure testing strategies, particularly in endemic regions.